Targeting the ventral pallidum in obesity

Obesity remains a global health challenge with escalating prevalence and imperfect treatments, necessitating novel therapeutic interventions. Hedonic feeding has been identified as a main driver of weight gain, leading to obesity. Therefore, targeting the neural circuits that regulate hedonic intake to reverse or treat obesity may boast a promising strategy. The ventral pallidum (VP), a crucial component of the brain's reward circuitry, plays a pivotal role in encoding reward value and reinforcing motivated behaviors, including food intake. This review highlights the work cementing the role of the VP in feeding regulation, and delves into the connectivity between the VP and other brain regions governing energy homeostasis and hedonic feeding behaviors. We also examine the evidence suggesting that dysregulation within the VP contributes to hyperphagia and the development of obesity. Lastly, we discuss the VP as a possible target for focused intervention. Deep brain stimulation for obesity has been under investigation for several years but current electrode targets yield mixed, dissatisfying results. While considerable progress has been made in elucidating the VP's role in feeding and obesity, several challenges remain in translating these findings into clinical interventions. Dissecting the diverse neurochemical, neuroanatomical, and projection connectivity of the VP will allow us to harness the full therapeutic potential of VP-based interventions, and may open avenues for developing targeted therapies to address the multifaceted nature of obesity.